Blood coagulation is important in the elaboration of the inflammatory response and in neoplastic growth and metastasis. Leukocyte procoagulants appear to have an important role in initiating coagulation in some of these disorders. Monocyte tissue factor (MTF), a cell associated procoagulant, is generated in increased amounts in patients with cancer and in decreased amounts in anticoagulated patients and normal volunteers. To allow a careful examination of in vivo regulation, we have developed a rabbit model for MTF generation. During the next year, the in vivo rabbit model of MTF generation will be further characterized in order to determine how closely it resembles the human system. Since studies to date demonstrate marked similarity between the human and rabbit systems, the animal model will be utilized to further examine the effect of neoplastic and inflammatory stimuli on in vivo MTF generation. The V2 carcinoma line is currently being utilized in this laboratory, and studies will be performed to determine whether MTF is generated in vivo after implantation of the malignant cell line. Additional studies will examine the regulation of MTF generation by T cells and soluble factors in tumor bearing animals. Similar studies will be performed utilizing inflammatory stimuli in place of neoplastic cells as the inducer of MTF generation. Such agents as specific antigens, LPS and immune complexes will be utilized to induce a variety of inflammatory responses in vivo and observe for either MTF generation in vivo or alteration of cellular or soluble regulators which might lead to enhanced MTF generation in vitro. Finally, further studies will be performed to determine the effect of pharmacological agents (warfarin, heparin and immunomodulators such as steroids or levamisole) on in vivo MTF generation. The in vitro fibroblast model of TF generation will also be utilized to further characterize the mechanisms involved in warfarin-mediated inhibition of TF generation.